Cardiac disease, including coronary heart disease (CHD) and associated heart failure following myocardial infarction (MI) comprises the most direct and indirect costs of major cardiovascular diseases [1]. Since the innate ability of the heart to repair itself following a MI is largely limited, regenerative therapies for patients with acute MI are being investigated as a means to reduce the extent of ischemic damage, whether as a novel treatment or a supplement to current therapies, such as primary percutaneous coronary intervention and thrombolytic therapy [2].
To successfully intervene in the heart's progressive functional decline with CHD, and specifically MI, there has been a large growth in clinical trials devoted to treat acute and chronic CHD. Multiple Phase II clinical trials, such as the TIME (NCT00684021) and LateTIME (NCT00684060) trials, have recently been conducted to help determine the appropriate timing of cell-based therapy to improve ventricular function and structure post-MI [3]. Specifically, the LateTIME trial was to evaluate the efficacy of cell treatment 2-3 weeks following initial MI in an effort to address high-risk patients with persistent LV dysfunction [3]. This has prompted the need to evaluate the efficacy of successful acute MI cellular therapies in a more clinically challenging model of established or chronic ventricular dysfunction.
Currently, there are many options as to which cell populations are under consideration for treatment of CHD. Of interest, adipose tissue houses an easily isolatable, regenerative, and multipotent cell population defined as the stromal vascular fraction (SVF), consisting of endothelial cells, smooth muscle cells, blood cells and mesenchymal cells containing perivascular and adventitial cells [4,5]. The broad clinical potential of SVF has significantly boosted the number of ongoing clinical trials utilizing adipose-derived cells as a cell therapy [6]. It is worth noting, though, most cell-based therapies are limited by the lack of retention of cells into the target tissue. In fact, one study found that only about 1.3-2.6% of transplanted cells could be detected in the infarcted myocardium in as little as 50-75 minutes after intracoronary injection [7]. However, by changing the delivery method to a cell-laden sheet (implanted onto the epicardium), greater post-infarct survival and greater cell engraftment has resulted compared to intramyocardial injections of the same cells [8]. Furthermore, others have shown that an epicardial cell sheet [8] can be implanted as long as 30 days post-MI and still result in improved angiogenesis and cell survival [9].